scholarly journals Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease

2018 ◽  
Vol 49 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
Niki Prakoura ◽  
Panagiotis Kavvadas ◽  
Christos E.  Chadjichristos
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Animal Models ◽  
Renal Disease ◽  
Connexin 43 ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Kidney Diseases ◽  
In Vivo Studies ◽  
Renal Diseases

Chronic kidney disease is an incurable to date pathology with a continuously growing incidence that contributes to the increase of the number of deaths worldwide. With currently no efficient prognostic or therapeutic options being available, the only possibility for treatment of end-stage renal disease is renal replacement therapy through dialysis or transplantation. Understanding the molecular mechanisms participating in the progression of renal diseases and uncovering the pathways implicated will permit the identification of novel and more efficient targets of therapy. Connexin43 was recently identified as a novel player in the development of chronic kidney disease. It was found de novo expressed and/or differentially localized in various renal cell populations during progression of renal disease, indicating an abnormal connexin signaling, both in patients and animal models. Subsequent in vivo studies demonstrated that connexin43 is involved in mediating inflammatory and fibrotic processes contributing to renal damage. Genetic, pharmaco-genetic or peptide-based inhibition of connexin43 in animal models and cell culture systems was successful in preventing the progression of the pathology and preserving the cell phenotypes. This review will summarize the recent advances on connexin43 in the field of kidney diseases and discuss the potential of future connexin43-based therapies against chronic kidney disease.

scholarly journals The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

2021 ◽  
pp. 1-17
Author(s):  
Hai Ning Wee ◽  
Jian-Jun Liu ◽  
Jianhong Ching ◽  
Jean-Paul Kovalik ◽  
Su Chi Lim
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Animal Models ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Kynurenine Pathway ◽  
T Cell Subsets ◽  
Renal Diseases ◽  
Tryptophan Degradation

<b><i>Background:</i></b> The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD<sup>+</sup>) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. <b><i>Summary:</i></b> This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD<sup>+</sup> production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. <b><i>Key Messages:</i></b> KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

scholarly journals Novel Targets for Therapy of Renal Fibrosis

2019 ◽  
Vol 67 (9) ◽  
pp. 701-715 ◽  
Author(s):  
Niki Prakoura ◽  
Juliette Hadchouel ◽  
Christos Chatziantoniou
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Renal Fibrosis ◽  
Connexin 43 ◽  
Cannabinoid Receptor ◽  
Experimental Models ◽  
Renal Diseases ◽  
Special Focus ◽  
Novel Targets ◽  
Stage Renal Disease

Renal fibrosis is an important component of chronic kidney disease, an incurable pathology with increasing prevalence worldwide. With a lack of available therapeutic options, end-stage renal disease is currently treated with renal replacement therapy through dialysis or transplantation. In recent years, many efforts have been made to identify novel targets for therapy of renal diseases, with special focus on the characterization of unknown mediators and pathways participating in renal fibrosis development. Using experimental models of renal disease and patient biopsies, we identified four novel mediators of renal fibrosis with potential to constitute future therapeutic targets against kidney disease: discoidin domain receptor 1, periostin, connexin 43, and cannabinoid receptor 1. The four candidates were highly upregulated in different models of renal disease and were localized at the sites of injury. Subsequent studies showed that they are centrally involved in the underlying mechanisms of renal fibrosis progression. Interestingly, inhibition of either of these proteins by different strategies, including gene deletion, antisense administration, or specific blockers, delayed the progression of renal disease and preserved renal structure and function, even when the inhibition started after initiation of the disease. This review will summarize the current findings on these candidates emphasizing on their potential to constitute future targets of therapy:

scholarly journals Seropositivity for Antibodies to DRS-G, a Virulence Factor from Streptococcus dysgalactiae subsp. equisimilis, Is an Independent Risk Factor for Poststreptococcus Glomerulonephritis and Chronic Kidney Disease in Mumbai, India

2015 ◽  
Vol 22 (8) ◽  
pp. 938-942 ◽  
Author(s):  
Gouri P. Hule ◽  
Mohan G. Karmarkar ◽  
Ainslie Cameron ◽  
Niwrutti Hase ◽  
Uday Khopkar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Streptococcus Dysgalactiae ◽  
Poststreptococcal Glomerulonephritis ◽  
Content Type ◽  
Esrd Patients

ABSTRACTThe disease spectrum caused byStreptococcus dysgalactiaesubsp.equisimilisresembles that ofS. pyogenes(group A streptococcus [GAS]). These two bacterial species are closely related and possess many common virulence characteristics. While some GAS strains express virulence factors called streptococcal inhibitor of complement (SIC) and distantly related to SIC (DRS), someS. dysgalactiaesubsp.equisimilisisolates express an orthologue of DRS, which is referred to as DRS-G. We reported previously that seropositivity for either anti-SIC or anti-DRS antibodies (Abs) is associated with poststreptococcal glomerulonephritis (PSGN). However, only seropositivity for anti-SIC Abs is associated with chronic kidney disease (CKD). We now extend the study to test whether seropositivity for anti-DRS-G Abs is also associated with these renal diseases. Stored serum samples collected for our previous study were tested by an enzyme-linked immunosorbent assay (ELISA) for Abs to DRS-G. The samples represented sera from 100 CKD adult patients, 70 adult end-stage renal disease (ESRD) patients, 25 PSGN pediatric patients, and corresponding age-matched control subjects. The proportion of PSGN, CKD, and ESRD patients who showed seroreaction to anti-DRS-G Abs was significantly higher than that of the corresponding age-matched controls, who in general exhibited seropositivity rates commensurate with the isolation rate ofdrsG-positiveS. dysgalactiaesubsp.equisimilisin the community during this study period. Since higher rates of seropositivity for anti-DRS-G Abs in the renal disease categories are resultant of previous infections with DRS-G-positiveS. dysgalactiaesubsp.equisimilisstrains, we conclude the seropositivity is an additional risk factor for these renal diseases. In this regard, anti-DRS-G Abs have attributes similar to those of the anti-SIC Abs.

scholarly journals VANTAGENS E DESVANTAGENS NA UTILIZAÇÃO DO QUESTIONÁRIO SCORED PARA TRIAGEM DE DOENÇA RENAL CRÔNICA EM PACIENTES NA ATENÇÃO BÁSICA: UMA REVISÃO DE LITERATURA

2021 ◽  
Author(s):  
Giovanna Benichel Bilancieri ◽  
Gabriela Beck Dos Santos ◽  
Letícia Umetsu Yaginuma ◽  
Eliazar Da Silva Santos Júnior ◽  
Eliane Cardozo Silva
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Diseases

Introdução: A doença renal crônica (DRC) é um grave problema de saúde pública, com alta prevalência, de 3 a 6 milhões de brasileiros, e mortalidade, de 15,7 por 100 mil ao ano. O rastreamento precoce em pacientes com comorbidades que predispõem à DRC, é infrequente no sistema único de saúde, resultando no diagnóstico tardio e prejuízos ao paciente. Pretendendo rastrear a DRC em fase inicial, foi elaborado o questionário SCORED, do inglês Screening for Occult Renal Disease. Constituído por 11 perguntas referentes a dados demográficos e clínicos, com pontuação de 0 a 12, sendo considerado paciente de alto risco para desenvolvimento de DRC aqueles com pontuação maior ou igual a 4. Objetivo: O presente estudo busca levantar as vantagens e desvantagens da utilização do questionário SCORED em pacientes da atenção primária à saúde. Materiais e métodos: Revisão baseada em artigos publicados no período de 2007 a 2021, nas plataformas LILACS e PubMed, a partir dos termos “Screening for Occult Renal Diseases” (15 e 5 artigos, respectivamente) e “SCORED and chronic kidney disease” (10 e 8 artigos, respectivamente). Posteriormente, foram excluídos os artigos incoerentes com o tema proposto e selecionados 9 trabalhos para a composição da revisão de literatura. Resultados: O método SCORED proporciona benefícios ao paciente, melhorando a qualidade de vida, acesso facilitado a medicamentos de alto custo e redução da mortalidade. A fácil aplicabilidade em contextos de assistência à saúde, meios de comunicação e a autoaplicação, somado ao baixo-custo, podem auxiliar a reduzir os gastos com tratamentos e terapia renal substitutiva. Todavia, o SCORED limita os fatores envolvidos na gênese da DRC, e considera o histórico médico autorrelatado, gerando alta sensibilidade e baixa especificidade. Ademais, necessita de confirmação por dosagem de creatinina sérica e taxa de filtração glomerular, que em idosos pode ser reduzida, devido ao declínio fisiológico. Conclusão: O questionário auxilia no diagnóstico precoce de DRC, sendo de fácil aplicação e custos baixos. Apesar disso, deve-se realizar o atendimento médico completo e exames complementares. Portanto, deve-se conscientizar que esse método de triagem carece de rastreio de outros quadros, como a doença renal policística autossômica dominante e glomerulonefrite.

scholarly journals B-mode gray-scale ultrasound abnormalities in adult patients: A useful tool in diagnosis of kidney diseases

2021 ◽  
Vol 11 (3) ◽  
pp. 97-102
Author(s):  
Kamel El-Reshaid
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Obstructive Uropathy ◽  
Reflux Nephropathy ◽  
Review Article ◽  
Renal Infarction ◽  
Ultrasound Scanning ◽  
Disease Prognosis

Ultrasound scanning of the urogenital tract has a pivotal role in revealing most etiologies of renal disease.  Moreover, it is also of value in assessment of disease prognosis and its progression.  In this review article, details of the examination technique, ultrasonic kidney norms and the clinicoradiological correlation regarding acute and chronic kidney disease are presented.  Specific characteristics of diseases viz. acute and chronic glomerulopathy, diabetes, amyloidosis, chronic reflux nephropathy, Nephroangiosclerosis, vasculitis, nephrocalcinosis, cystic diseases of the kidney, renal infarction and obstructive uropathy are presented. Keywords: acute, chronic, diagnosis, diseases, ultrasound, kidney.

SGLT2 inhibition for cardiovascular diseases, chronic kidney disease and NAFLD

Endocrinology ◽  
2021 ◽  
Author(s):  
Moein Ala
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Signaling Pathways ◽  
Observational Studies ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Renal Diseases ◽  
Beneficial Effects

Abstract Sodium glucose cotransporter 2 (SGLT-2) inhibitors are the latest class of anti-diabetic medications. They prevent glucose reabsorption in the proximal convoluted tubule to decrease blood sugar. Several animal studies revealed that SGLT-2 is profoundly involved in the inflammatory response, fibrogenesis and regulation of numerous intracellular signaling pathways. Likewise, SGLT-2 inhibitors markedly attenuated inflammation and fibrogenesis and improved the function of damaged organ in animal studies, observational studies and clinical trials. SGLT-2 inhibitors can decrease blood pressure and ameliorate hypertriglyceridemia and obesity. Likewise, they improve the outcome of cardiovascular diseases such as heart failure, arrhythmias and ischemic heart disease. SGLT-2 inhibitors are associated with lower cardiovascular and all-cause mortality, as well. Meanwhile, they protect against non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), acute kidney injury (AKI), and improve micro- and macroalbuminuria. SGLT-2 inhibitors can reprogram numerous signaling pathways to improve NAFLD, cardiovascular diseases and renal diseases. For instance, they enhance lipolysis, ketogenesis, mitochondrial biogenesis and autophagy while they attenuate renin-angiotensin-aldosterone system (RAAS), lipogenesis, endoplasmic reticulum (ER) stress, oxidative stress, apoptosis and fibrogenesis. This review explains the beneficial effects of SGLT-2 inhibitors on NAFLD, cardiovascular and renal diseases and dissects the underlying molecular mechanisms in detail. This narrative review explains the beneficial effects of SGLT-2 inhibitors on NAFLD, cardiovascular and renal diseases using the results of latest observational studies, clinical trials and meta-analyses. Thereafter, it dissects the underlying molecular mechanisms involved in the clinical effects of SGLT-2 inhibitors on these diseases.

scholarly journals Deprivation and kidney disease—a predictor of poor outcomes

2019 ◽  
Vol 13 (2) ◽  
pp. 128-132
Author(s):  
Greg D Guthrie ◽  
Samira Bell
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Confounding Factors ◽  
Growing Body ◽  
Poor Outcomes

Abstract There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of Clinical Kidney Journal, Hounkpatin et al. describe the association of socioeconomic deprivation with incidence, mortality and resolution of AKI in a large UK cohort. Investigating deprivation as a factor influencing either incidence or outcome of disease is challenging due to variations in measures of deprivation used and other confounding factors that may be contributing to the observed differences. In this editorial, we review the current literature examining the role of deprivation in renal disease.

scholarly journals Renal biopsy findings during and after pregnancy

2019 ◽  
Vol 13 (4) ◽  
pp. 174-178
Author(s):  
Frances Conti-Ramsden ◽  
Paul Bass ◽  
Lucy C Chappell ◽  
Kate Bramham
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Biopsy ◽  
De Novo ◽  
Health Centre ◽  
Reproductive Age ◽  
Free Text ◽  
Renal Biopsies ◽  
Stage Renal Disease

Background Chronic kidney disease is estimated to affect up to 6% of women of reproductive age. Maternity care represents an opportunity for early diagnosis but there is limited understanding of chronic kidney disease aetiology occurring in or revealed by pregnancy. Methods A retrospective evaluation of renal biopsies during and after pregnancy between 2000 and 2015 was undertaken. A large academic health centre pathology database was searched for free text pregnancy-related terms, restricted to typology code 71000 (kidney). Indications and findings of postpartum renal biopsies were reviewed. Results Sixty-three renal biopsy reports were identified. Of 45 biopsies performed postpartum, 34 (75.6%) investigated persistent postpartum proteinuria. 20/34 (70.6%) of these biopsies yielded a primary renal disease, and 6/34 (17.6%) women had progressed to end stage renal disease at latest follow-up. Conclusion Renal biopsy findings of women investigated for persistent postpartum proteinuria revealed a high incidence of histological diagnosis of de novo renal disease.

scholarly journals Chronic Kidney Diseases in Children, Management Difficulties and Amelioration in Bangladesh: A Review

2017 ◽  
Vol 7 (1) ◽  
pp. 26-32
Author(s):  
Ranjit Ranjan Roy ◽  
Abdullah Al Mamun ◽  
M Abdul Matin ◽  
Md Rafiqul Islam
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Care Delivery ◽  
Limited Resource ◽  
Health Care Delivery System ◽  
National Registry ◽  
Government Organizations ◽  
Stage Renal Disease

Background: Bangladesh is a small country of south Asia with a population of 153 million, among them 66 million are under age of 18years. The exact prevalence of chronic kidney disease (CKD) in children is not well known due to lack of a national registry. But in Bangabandhu sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, the incidence is 7.9% in 2013 and there are approximately thirty five hundred thousand around the country. There are 4.4% of children with renal disease prevalent in the country. But unfortunately, there is diagnostic problem and the treatment facility is very limited. Only few centers provide the renal replacement therapy in this country and only two centers do pediatric renal transplantation. So, to tackle this large burden with very limited resource, it is important to try and reduce the incidence of chronic kidney disease, especially end stage renal disease. We can handle the present situation with our existing resource with some modification of health care delivery system with contribution from government, non government organizations (NGO'S) and affluent people. This article highlights chronic kidney disease in children, present treatment modality and some fiiture directive to handle such a crucial problem, thus may help thousands of children from such a devastating situation.J Shaheed Suhrawardy Med Coll, 2015; 7(1):26-32

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